Calcium homeostasis

1. CALCIUM HOMEOSTATIS

2. OVERVIEW
Intro.
Absorption.
Function.
Regulation of calcium homeostasis:
PTH.
Vitamin D.
Calcitonin.
Hypocalcaemia.
Hypercalcaemia.
References.

3. INTRO
Fifth most common element in the body.
99% present in skeleton (reservoir).
1% intracellular.
0.1% extracellular.
Forms of Ca in the blood:
50% is free ionised calcium.
40% is protein bound (mainly albumin).
10% is complexed to small diffusible ligands (e.g. bicarbonate,
citrate, phosphate, lactate and sulphate).
Normal level 2.20 -2.6 mmol/L.

4. ABSORPTION
Widely distributed in food substances e.g. Milk, Cheese, Egg-yolk,
Fish , Beans, and Lentils.

The 2 mechanisms of intestinal absorption of calcium are:
Active: is a saturable, transcellular process which involves calbindin
(calcium-binding protein) – regulated by the active form of vitamin D.
Passive: is a nonsaturable, paracellular low efficiency process, which is
not affected by calcium status or parathyroid hormone.
Both processes occur throughout the small intestine.
 Absorption is related to calcium intake.

5. ABSORPTION

Factors stimulating calcium absorption:
An acidic pH.
High protein diet – Lysine and Arginine cause maximal absorption.
Presence of vitamin D.
State of health and intact mucosa.
PTH stimulates the activation of vitamin D, consequently indirectly
increasing absorption of Calcium.

6. ABSORPTION
Factors inhibiting calcium absorption:
Alkaline pH
High fat diet – fatty acids form calcium soaps that cannot be
absorbed.
Excess phosphates, magnesium and iron.
Glucocorticoids reduce intestinal absorption of calcium.
Calcitonin decreases calcium absorption indirectly by inhibiting the
activation of vitamin D.
Advancing age and intestinal inflammatory disorders.

7. FUNCTION
 Major structural element in the bones and teeth.
Essenial for several physiological processes such as neuromuscular
transmission, smooth, skeletal, and cardiac muscle contractions,
nerve function, and cell division and movement.
Co-factor in Blood coagulation.
Plays an important role in the action of other intracellular
messengers e.g. cyclic adenosine monophosphate (cAMP) and
Inositol -triphosphate, which are responsible for mediating the
cellular response to various hormones including epinephrine,
glucagon, ADH, and secretin.
Release of neurotransmiters and hormones.

8. REGULATION OF CALCIUM HOMEASTASIS
The 3 main hormones involved in the homeostatic regulation:
PTH
Vitamin D
Calcitonin
Acting at 3 target organs: intestine, bone and kidneys.

9. PTH
Polypeptide containing 84 amino acids residues.
Secreted by the chief cells in the 4 parathyroid glands.
Part of a negative feedback loop to maintain calcium ions in the
extracellular fluid.
In hypocalcaemia, parathyroid hormone secretion is stimulated.
In hypercalacaemia, secretion is inhibited, and the calcium is deposited in the
bones.
PTH increases serum calcium levels through:
Increasing bone resorption by activating osteoclastic activity.
Increasing renal calcium reabsorption by the distal renal tubules.
Increasing renal phosphate excretion by decreasing tubule phosphate reabsorption.
Increasing the synthesis of 1,25-dihydroxyvitamin D (also called calcitriol) by
increasing the activity of alpha-hydroxylase enzyme in the kidney.

10. VITAMIN D


Group of closely related sterols produced by the action of UV
light.

Vitamin D3 (also called Cholecalciferol) is produced by the
action of sunlight and is hydroxylated to 25-hydroxy-
cholecalciferol (25-HCC) in the liver.

Further hydroxylation of 25-HCC occurs in the proximal
tubules of the kidney to form the active metabolite, 1,25-
hydroxy-cholecalciferol (1,25-DHCC) or calcitriol.

Calcitriol's formation is facilitated by PTH.

11. VITAMIN D
V
Vitamin D maintains calcium homeostasis by:
-
-Increasing calcium absorption from the intestine (by interacting with a
calcitriol receptor located in intestinal epithelial cells.
S
-Stimulating renal tubular reabsorption of calcium.
I
-Increasing bone calcification and mineralisation (by acting on
osteoclasts in the bone)

12. CALCITONIN
 32 amino acid polypeptide secreted by the parafollicular cells in
the thyroid gland.
 Major stimulus for calcitonin secretion is increased serum calcium.
The major action of calcitonin is to inhibit osteoclastic bone
resorption, which decreases the serum calcium concentration.
Clinical use:
Used in the treatment of Paget's diease.

13. CAUSES AND SYMPTOMS OF
HYPOCALCAEMIA
Causes:
Hypoalbuminaemia,
Hypoparathyroidism
(idiopathic,surgical, or
transient)
Magnesium deficiency
(alcoholism, chemotherapy
treatment)
Pseudohypoparathyroidism
Vitamin D deficiency
Malnutrition
Renal insufficiency
Acute pancreatitis
Bacterial/viral infections.
Drugs including
anticonvulsants (e.g.
phenytoin, phenobarbital and
rifampin)
Symptoms:
Asymptomatic.
Neurological (tingling,
tetany, mental changes)
Muscle cramps (changes in
muscle excitability)
Cardiac signs (abnormal
ECG)
Seizure

14. CAUSES OF HYPERCALCAEMIA
PTH mediated:
Primary hyerparathyroidism.
Lithium induced.
Tertiary hyperparathyroidism.
Calcitriol mediated:
Granulomatous disease.
Milk alkali syndrome.
Exogenous Vitamin D.
Other causes:
Vitamin A toxicity.
Paget's disease.
Kidney stones.
Adrenal insufficiency.
Cancer:
Multiple myeloma.
 PTHrp mediated-Breast, lung,
renal cancer.
Bone metastases.

15. SYMPTOMS OF HYPERCALCAEMIA
Neurological & psychiatric (lethargy,
confusion, irritability, depression).
GI issues (anorexia, abdo pain, nausea
& vomiting, constipation).
Renal issues (polyuria, renal stones).
Muscoskeletal issues (bone/joint pain,
muscle weakness, cardiac
arrhythmias).

16. DIAGNOSIS
Total (amended) Calcium
amended[Ca]=measured total[Ca]+0.02(40-[albumin])
Albumin
PTH ( high hypocalcaemia, low hypercalcaemia)
Vitamin D (high hypocalcaemia, low hypercalcaemia)
LFT (ALP is raised hypercalcaemia and normal in hypocalcaemia)
(Phos raised in hypocalcaemia and low in hypercalcaemia)
U&E (urea and creatinine increased in hypercalcaemia)
Iron (raised in hypocalcaemia)
PH (Acidosis increases calcium and alkalosis decreases calicum)
24-hour urinary calcium (elevated in hyperparathyroidism, renal
failure and decreased in hypoparathyroidism, malabsorption disorders)

17. TREATMENT
H
Hypocalcaemia:
O
ral calcium and vitamin D
supplements and Mg
supplements (mildly
symptomatic and chronic
hypocalcaemia).
I
ntravenous calcium gluconate
(acute symptomatic
hypocalcaemia).
)
Y
Hypercalcaemia:
M
Mildly symptomatic patients (3.0 – 3.5
mmol/L) must avoid factors that can
aggravate hypercalcemia, e.g. thiazide
diuretics and lithium carbonate
therapy, and a high calcium diet.
C
Ca >3.5mmol/Lalways requires urgent
treatment, including volume expansion
with isotonic saline, administration of
salmon calcitonin and zoledronic
acid .
F
Follow-up therapy to treat underlying
disease e.g. Cancer.

18. References

Baynes J. (1999) Medical Biochemistry. Basildon.Harcourt Brace and
Company Limited.

Baker S. et al.(2002) The essentials of Calcium, Magnesium and Phosphate
Metabolism. Critical Care and resuscitation. 4(4) pp. 301-306.[online]

Nessar A. (2010) Clinical Biochemistry. New York. Oxford University Press.

Mundy G. et al. (1999) Hormonal Control of Calcium Homeostasis, Clinical
Chemistry, 45 (8), pp.1347-1352.

Warrel D. et al.(2003) Oxford Textbook of Medicine. London.Oxford University
Press.[online]

Peacock M. (2010) Calcium Metabolism in Health and Disease, Clinical
Journal of American Society of Nephrology,5(1), pp. 23-30.[online]